Hair Wars

This article reports that few scientists go further than Stephen Barker to keep his experimental subjects content. A parasitologist at the University of Queensland in Brisbane, he studies head lice. So when it comes to mealtimes, Barker tapes a pill box with the bottom removed to one of his legs, pops in the insects, and lets them tuck in. Head lice, nits, cooties, or Pediculus humanus call them what you will, they may seem like a medieval health problem that we should have licked by now. But as beleaguered parents know, we are a long way from winning the war against head lice. INSET: Of lice and men.

They have sucked our blood for millennia, resisting all efforts to defeat them. What’s next in the battle against head lice?

FEW scientists go further than Stephen Barker to keep his experimental subjects content. A parasitologist at the University of Queensland in Brisbane, he studies head lice. These creatures only have one food source : blood. Human blood, to be precise, and they like it fresh. “It’s ironic,” says Barker. “They’re bastards to kill when they’re on people and bastards to keep alive when they’re not.”

So when it comes to mealtimes, Barker tapes a pill box with the bottom removed to one of his legs, pops in the insects, and lets them tuck in. It is not a pleasant experience, he says. “You can feel the sting as each one bites but it’s the only way to keep the suckers alive.”

Head lice, nits, cooties, or Pediculus humanus call them what you will, they may seem like a medieval health problem that we should have licked by now. But as beleaguered parents know, we are a long way from winning the war against head lice. Cases appear to be on the up in many countries, including the UK. Lice rapidly evolve resistance to the chemical insecticides used to kill them, while physical methods of removing the bloodsuckers are tiresome and time-consuming so are often not carried out properly. All it takes is one child with a few lice surviving for a whole school to be re-infested, so parents can face a never-ending battle.

Fortunately a number of sophisticated new strategies against these parasites are on the horizon. We are discovering the louse genes responsible for insecticide resistance, so the beasts could be targeted region by region with chemicals to which they are vulnerable. There’s a drug in development that works against a crucial louse enzyme, and other new agents that block up their breathing holes. Those pesky critters aren’t going to know what’s hit them.

Perhaps it is scarcely surprising that the humble head louse is so hard to get rid of. After all, it has lived on us for millions of years (see “Of lice and men”, page 67) ample time to become extremely good at hanging on.

Lice are almost invariably caught by being in close head contact with someone who is infested. The females lay between one and 10 eggs a day (these are the “nits”), so lice numbers can quickly build. A child with head lice typically hosts between 10 and 100 of the beasts, though in bad cases there can be many hundreds crawling around.

Although head lice cause no serious medical problems, infested humans mount an immune response to louse saliva which can cause swollen lymph glands. The itchiness may affect concentration in school, and some kids end up with bloody sores from all that scratching. “If you have 100 lice biting you all night, you are not going to sleep,” says Barker.

Getting an accurate fix on infestation rates is notoriously difficult, as people tend to keep quiet if they or their children are affected. But in the UK, until the mid-1990s, headlice insecticides were only available on prescription, providing a means of tracking the problem. Between 1980 and 1995, the number of prescriptions written rose 37-fold. And there’s no reason to think the numbers have fallen since then. In 2002, a random sampling of schools in Bristol found that between 10 and 40 per cent of 7-year-olds were infested. There are signs of similar trends in Australia and parts of the US.

The main weapon against lice is a group of insecticides that work by overstimulating the nervous system, causing paralysis and death. They are less effective against the eggs, so most need a second application after a week to kill any newly hatched lice. Commonly used products contain pyrethrins a group of compounds extracted from chrysanthemum plants or their synthetic and longer-lasting equivalents called pyrethroids. If these don’t work, the next step is usually an organophosphate called malathion.

But lice, just like bacteria, have an awesome ability to evolve resistance to the chemicals used to kill them. And as with bacteria, the problem is made worse when people fail to complete the treatment, increasing the chance that survivors remain to pass on their resistance.

Once it develops, resistance can quickly spread through communities. Cure rates for permethrin and phenothrin, popular pyrethroids, have fallen well below 50 per cent in parts of the UK. Lab tests show some parts of the country are home to superlice that are resistant to five different chemicals, including malathion. Studies by Barker’s team suggest that a similar situation may be emerging in Australia. Resistance to pyrethrins and pyrethroids is also rife in parts of the US, though malathion appears to be holding its own, probably because it is used less frequently.

An alternative to chemicals is wet-combing, sometimes called “bug-busting”. This involves coating the hair with conditioner, clipping it into sections and painstakingly combing through it using an extremely fine-toothed comb. It is growing in popularity among parents who are reluctant to douse their kids in chemicals, although pyrethrins and pyrethroids are considered to be pretty safe as they break down quickly. But combing needs to be done four times over two weeks as it cannot pick out the eggs, and it can be extremely time-consuming, especially in large families of long-haired individuals. “If you have a couple of kids with short, straight hair who don’t put up a fight, then it’s a winner. But that’s not a normal family,” says Anthony Downs, a dermatologist at the Royal Devon and Exeter Hospital in the UK. Indeed, the only controlled clinical trial of bug-busting found that it was successful in only about half the participants.

Alternative therapies, such as electric nit combs and essential oils, have yet to be proven in large randomised clinical trials. “Some have never even been tested under lab conditions,” says Christine Brown, a nurse at Insect Research and Development, a medical entomology company in Hertfordshire, UK. “Their effectiveness is mostly hearsay.”

So what is to be done? According to John Clark of the University of Massachusetts Amherst, some serious “resistance management” akin to that used for agricultural pesticides is needed. A classic approach would be to use chemicals in rotation so lice resistant to one would succumb to others that kill by different means. This method would probably be impractical outside a controlled farm environment, however, as it entails persuading people en masse to use the same chemical. An alternative could be to use the chemicals in combination. This would reduce the chances of resistant lice emerging in the first place because they would need to acquire numerous mutations simultaneously.

Clark’s team recently pinpointed some of the key genetic mutations that make head lice resistant to pyrethrins and pyrethroids (Pesticide Biochemistry and Physiology, vol 75, p 79, and vol 77, p 115). They change the shape of a molecule in the cell membrane of louse neurons that the insecticides normally bind to, thus preventing the binding. The researchers have also found two mechanisms for malathion resistance. They have not yet published details, but Clark says one involves destroying the molecule more efficiently, while the other slows the process that converts malathion into its active form.

These findings could make it easier to work out which insecticides lice are resistant to at a local level. At the moment, resistance monitoring is not widely practised because it is time-consuming and difficult. It involves taking lice from infested heads and often having to keep them alive in feeder cups such as Barker’s until they can be exposed to insecticides to see how quickly they die. “Getting live lice from one place to another is a real problem, unless you are prepared to become infested,” says Clark. But once all the main mutations are known, resistance monitoring could be done through DNA testing, for which live insects would not be needed. Clark has already developed a DNA test for his three mutations that give resistance to pyrethrins and pyrethroids. In future it may be commonplace for schools and pharmacists to keep information on which products work locally and which don’t.

But we also need better ways of killing lice. One new approach involves suffocation. Like other insects, head lice breathe through a series of portholes along the sides of their bodies known as spiracles. Plenty of home remedies are supposed to smother lice by bunging up their spiracles, but they are usually of dubious efficacy and very messytry coating a child’s head in mayonnaise or petroleum jelly. As well as the fact that kids will wipe off the gunk on pillows, towels and each other, head lice with blocked spiracles can survive for up to six hours, according to recent research by Dale Pearlman, a dermatologist in Menlo Park, California.

He has come up with a novel suffocating agent that dries on the hair and so could be more likely to stay on long enough to work. During treatment, the hair looks completely normal, says Pearlman, who is trying to develop the lotion commercially. The product contains cetyl alcohol and stearyl alcohol. When applied to the hair and then dried with a hair-dryer, these chemicals effectively shrinkwrap the head lice, blocking their spiracles until the lotion is washed off 8 hours later.

In the first clinical trial of this product, which was published in September, 133 people, mainly children, were treated once a week for three weeks (Pediatrics, vol 114, p 275). There was ago per cent cure rate, although there was no control group, and Pearlman acknowledges the parents in the study may have been particularly well motivated to stick with the treatment, as they had to put down a $200 deposit that was refunded at the end.

Another new agent that may work by blocking spiracles also seems to be fairly successful. At the 2003 American Academy of Dermatology meeting in San Francisco, Downs reported that in a double-blind randomised controlled clinical trial, a coconut-derived emulsion sold in natural food stores in the US cured 60 per cent of children treated. The mechanism is unknown but it may be that the oil droplets in the emulsion can block the lice spiracles. “It’s very promising,” says Downs. “It would be difficult for lice to adapt their anatomy to develop resistance.”

Keep it simple
The suffocating treatments are not the only new approaches in the pipeline. A key goal in the battle against lice is to develop something that works against eggs. While several popular brands of louse insecticide are claimed to kill the lice in the eggs as well as the adults, in practice they tend to be less effective against eggs, in part because early embryos lack the nervous system these chemicals target. But if an agent that targets eggs could be developed and combined in one lotion with an insecticide that kills adults it would avoid the need for two applications. And the simpler the treatment, the likelier it is that parents will carry it out successfully and break the recurring infestation cycle.

A group of scientists at the University of Melbourne, Australia, are interested in the enzymes known as proteases that enable lice to hatch. They have identified several inhibitors that block these enzymes, and have founded a biotech firm, Hatchtech, to commercialise the most effective ones. In their tests, all eggs between one and five days old failed to hatch when treated with the inhibitors, compared with hatch rates of between 40 and 100 per cent for eggs treated with commercially available insecticides. “We believe we are targeting multiple proteases, not just one, so it should significantly delay the time until resistance may be a problem,” says Vern Bowles, chief scientific officer of Hatchtech. The firm hopes to start human trials within two years.

Another possible strategy under consideration is to repel head lice, much as we do mosquitoes. Several products are sold as head louse repellents or are recommended for this purpose. They include tea tree, lavender, peppermint and neem seed oils. But Deon Canyon at lames Cook University in Queensland, Australia, has tested seven such substances, as well as DEET, a common insect repellent, and not one was effective. “It was a myth-busting exercise,” says Canyon. “So far the evidence suggests repellents don’t work.” But the fact that some children remain louse-free despite sitting next to children with lots of lice suggests that a repellent is theoretically possible, he says.

It may be some time, then, before we find the the ultimate weapon in head louse warfare: a product that kills both nits and cooties as well as repelling incomers. In the meantime, better education about lice and their habits would at least focus efforts on activities that actually work. Recent research suggests that common advice to boilwash victims’ clothes and bed linen, and vaccum the whole house is probably misguided.

If all else fails there is always one cheap, easy failsafe that is both cure and repellent head shaving. Now try getting your kids to cooperate with that.

“Some superlice are resistant to as many as five different chemicals”

“Try coating a child’s head in mayonnaise or petroleum jelly”

PHOTO (COLOR): Hooked on you: the electron microscope reveals how a head louse grips a hair, alongside an egg, or nit

PHOTO (COLOR): Children catch lice easily. Between 10 and 40 per cent of 7-year-olds in the UK could be infested

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By Rachel Nowak

Of Lice and Men

THERE is one reason to be thankful for head lice. Our long-term relationship with them may have something to teach us about our own evolution.

The oldest head-louse egg to be discovered was found attached to a 10,000-year-old human hair at an archaeological site in north-east Brazil (Parasitology Today, vol 16, p 269). But the louse-human partnership goes back much further.

David Reed, an evolutionary biologist at the University of Florida, Gainesville, and his colleagues have used DNA analysis to show that two genetically distinct strains of head louse emerged about 1.2 million years ago, around the time of the split between Homo erectus and the lineage that would become Homo sapiens (Public Library of Science Biology, vol 2, p 1972). Reed reckons the head lice strains are too different to have evolved on the same host species. One must have spent the last 1.2 million years on H. sapiens and the other on H. erectus, only to move back to H. sapiens around 25,000 years ago. As lice need dose physical contact to move from person to person, the team claims its findings suggest that this was the case with H. erectus and H. sapiens.

Another study by researchers at the Max Planck Institute for Evolutionary Anthropology in Leipzig, Germany, used DNA analysis to find out when body lice, which live on clothing, evolved from head lice (Current Biology, vol 13, p 1414). They came up with the figure of 72,000 years ago, suggesting a relatively recent date for the adoption of clothing that correlates with the spread of modern humans out of Africa to colder climes.

*The author cited above is not in any way affiliated with Rainforest Essentials. Their citation is offered solely for informational purposes and not to be construed as an endorsement of Lice Off!™ in particular or any of our products in general.